System and method of adjusting the compliance voltage in a neuromodulation device

ABSTRACT

A therapeutic neuromodulation system configured for providing therapy to a patient. The therapeutic neuromodulation system comprises a plurality of electrical terminals configured for being respectively coupled to a plurality of electrodes implanted within tissue, analog output circuitry configured for delivering therapeutic electrical energy between the plurality of electrical terminals in accordance with a set of modulation parameters that includes a defined current value, a voltage regulator configured for supplying an adjustable compliance voltage to the analog output circuitry, and control/processing circuitry configured for automatically performing a compliance voltage calibration process at a compliance voltage adjustment interval by periodically computing an adjusted compliance voltage value as a function of a compliance voltage margin. The control/processing circuitry may also be configured for automatically adjusting at least one of the compliance voltage adjustment interval and the compliance voltage margin during the compliance voltage calibration process.

CLAIM OF PRIORITY

The present application is a continuation of U.S. application Ser. No.15/421,926, filed Feb. 1, 2017, now U.S. Pat. No. 10,307,595, issuedJun. 4, 2019, which is a continuation of U.S. application Ser. No.14/464,557, filed Aug. 20, 2014, now U.S. Pat. No. 9,616,233, issuedApr. 11, 2017, which claims the benefit under 35 U.S.C. § 119 to U.S.provisional patent application Ser. No. 61/871,793, filed Aug. 29, 2013.The foregoing applications are hereby incorporated by reference into thepresent application in their entirety.

FIELD OF THE INVENTION

The present inventions relate to tissue modulation systems, and moreparticularly, to programmable neuromodulation systems.

BACKGROUND

Implantable neuromodulation systems have proven therapeutic in a widevariety of diseases and disorders. Pacemakers and Implantable CardiacDefibrillators (ICDs) have proven highly effective in the treatment of anumber of cardiac conditions (e.g., arrhythmias). Spinal CordStimulation (SCS) systems have long been accepted as a therapeuticmodality for the treatment of chronic pain syndromes, and theapplication of tissue stimulation has begun to expand to additionalapplications such as angina pectoralis and incontinence. Deep BrainStimulation (DBS) has also been applied therapeutically for well over adecade for the treatment of refractory chronic pain syndromes, and DBShas also recently been applied in additional areas such as movementdisorders and epilepsy. Further, in recent investigations, PeripheralNerve Stimulation (PNS) systems have demonstrated efficacy in thetreatment of chronic pain syndromes and incontinence, and a number ofadditional applications are currently under investigation. Furthermore,Functional Electrical Stimulation (FES) systems have been applied torestore some functionality to paralyzed extremities in spinal cordinjury patients.

Each of these implantable neuromodulation systems typically includes atleast one neuromodulation lead implanted at the desired modulation siteand an neuromodulation device, such as an implantable pulse generator(IPG), implanted remotely from the modulation site, but coupled eitherdirectly to the neuromodulation lead(s), or indirectly to theneuromodulation lead(s) via one or more lead extensions. Thus,electrical pulses can be delivered from the neuromodulation device tothe electrodes carried by the neuromodulation lead(s) to modulate avolume of tissue in accordance with a set of modulation parameters andprovide the desired efficacious therapy to the patient. Theneuromodulation system may further comprise a handheld remote control(RC) to remotely instruct the neuromodulator to generate electricalmodulation pulses in accordance with selected modulation parameters. TheRC may, itself, be programmed by a technician attending the patient, forexample, by using a Clinician's Programmer (CP), which typicallyincludes a general purpose computer, such as a laptop, with aprogramming software package installed thereon.

Electrical modulation energy may be delivered from the neuromodulationdevice to the electrodes in the form of an electrical pulsed waveform.Thus, electrical modulation energy may be controllably delivered to theelectrodes to modulate neural tissue. The configuration of electrodesused to deliver electrical pulses to the targeted tissue constitutes anelectrode configuration, with the electrodes capable of beingselectively programmed to act as anodes (positive), cathodes (negative),or left off (zero). In other words, an electrode configurationrepresents the polarity being positive, negative, or zero. Otherparameters that may be controlled or varied include the amplitude,width, and rate of the electrical pulses provided through the electrodearray. Each electrode configuration, along with the electrical pulseparameters, can be referred to as a “modulation parameter set.”

With some neuromodulation systems, and in particular, those withindependently controlled current or voltage sources, the distribution ofthe therapeutic electrical current between the electrodes (including thecase of the neuromodulation device, which may act as an electrode) maybe varied such that the current is supplied via numerous differentelectrode configurations. In different configurations, the electrodesmay provide current or voltage in different relative percentages ofpositive and negative current or voltage to create different electricalcurrent distributions (i.e., fractionalized electrode configurations).

More pertinent to the present inventions, a neuromodulation device mayinclude one or more current sources/sinks that are configured tosupply/receive therapeutic electrical current to/from the electrodes.For example, as shown in FIG. 1, a basic output current source 1 and acorresponding output current sink 2 used to deliver electrical energy totissue exemplified generically as a load resistance R will be described.The output current source 1 includes a current generator 3,digital-to-analog circuitry (DAC) 4, and a selection transistor 5.Likewise, the output current sink 2 includes a current generator 6, aDAC 7, and a selection transistor 8.

Each of the current generators 3, 6 includes transistors M1, M3 eachconfigured for generating a reference current I_(ref). Each of the DACs4, 7 is configured for scaling the reference current I_(ref) using aparallel number N of transistors M2, M4. It should be appreciated thateach of the transistors M1/M3 and transistors M2/M4 can be consideredcurrent mirrors. The transistors M1, M3 in the output current source 1are P-type transistors, and thus, the DAC 4 can be considered a PDAC,and similarly, the output current source 1 can be considered PDACcircuitry. In contrast, the transistors M2, M4 in the output currentsink 2 are N-type transistors, and thus, the DAC 7 can be considered anNDAC, and similarly, the output current sink 2 can be considered NDACcircuitry. Without a full discussion of transistor physics, one skilledin the art will recognize that use of transistors of such polarities issensible, given that the output current source 1 will be tied to apositive voltage (V+, referred to herein as the “compliance voltage”),while the output current sink 2 will be tied to a more negative voltage,such as ground. A “ground voltage” as used herein should be understoodas any reference voltage with respect to the compliance voltage.

Each of the selection transistors 5, 8 selects the number of outputstages M2, M4 to be activated in the respective DACs 4, 7 in response tothe input of a digital signal. Therefore, the DAC 4 may scale thereference current I_(ref) by the selected number j to source an outputcurrent I_(out) equal to j*I_(ref) to electrode E_(x), and the DAC 7 mayscale a selection transistor 5 by the selected number k to sink an inputcurrent I_(in) equal to k*I_(ref) from electrode E_(y). Thus, the outputcurrent source 1 and output current sink 2 are generally digitallycontrollable by the selection transistors 5, 8 to respectively generatethe output current I_(out) and input current I_(in). If the electrodesE_(x), E_(y) are the only electrodes utilized by the neurostimulator,the current I_(out) at E_(x) will be equal to the current I_(in) atE_(y). However, as is typical, more than two electrodes may be used, inwhich case the output current sourced to a particular electrode may notbe equal to the output current sunk into another electrode. In any case,the sum of the output current I_(out) sourced by any number ofelectrodes will be equal to the sum of the input current I_(in) sunk toany number of electrodes

As just alluded to, a neuromodulator typically operates with severalelectrodes, and the various current sources and sinks can be controlledto source or sink current to any particular electrode as is efficaciousfor treating a particular patient. Different output source/sinkarchitectures can be used in a neuromodulation device. For example, eachelectrode can be coupled to dedicated PDAC/NDAC circuitry, which allowsthe electrode to either operate as a current source or a current sink,as described in U.S. Pat. No. 6,181,996, which is expressly incorporatedherein by reference. As another example, PDAC/NDAC circuitry can beselectively coupled to any of the electrodes via a low-impedanceswitching matrix, as described in U.S. Pat. No. 6,516,227, which isexpressly incorporated herein by reference. As still another example,instead of using discrete PDAC and NDAC blocks that services the variouselectrodes, the PDAC and NDAC circuitry is effectively distributed suchthat any of a number of current mirrors can be coupled to any of theelectrodes, as described in U.S. patent application Ser. No. 11/177,503,which is expressly incorporated herein by reference.

Regardless of the current source/sink architectures used, all generallyhave similar current output path characteristics. That is, referringback to FIG. 1, the current output paths in each architecture comprises,at a minimum, a current source output transistor (or transistors ifparalleled for current gain) 3, a selection transistor 5 to control theflow of the current source transistor(s) 3, the load resistance R, acurrent sink transistor (or transistors if paralleled for current gain)6, and a selection transistor 7 to control the flow of the current sinktransistor(s) 6. Each of these elements has some resistance, and hencesome amount of the compliance voltage V+ will be dropped across theseelements when current is flowing through the load resistance R.Specifically, the compliance voltage V+ will equal V_(DS1)+VR+V_(DS2),where V_(DS1) is the drain-to-source voltage drop across the currentsource transistor(s) 3 and the selection transistor 4, and V_(DS2) isthe drain-to-source voltage drop across the current sink transistor(s) 6and the selection transistor 7, and V_(R) equals the voltage drop acrossthe load resistance R.

It should be appreciated that the M1/M3 and M2/M4 current mirrorsrequire that transistors M1 and M2 operate in saturation mode, such thatthe channels of the transistors are in “pinch off,” as illustrated inFIG. 2. When in the saturation mode, the output current I_(out) isproportional to the gate voltage of the transistors M1 or M2, but doesnot depend upon the drain voltage to the first order. However, to keepthe transistors M1 and M2 in the saturation mode, a certaindrain-to-source voltage V_(DS) has to be satisfied for each transistor.

What this means in the context of the output current circuitry of FIG. 1is that the circuit can operate properly over a range of compliancevoltages V+. For example, suppose a suitable therapy for a patientsuggests that a current of I_(out)=5 mA should be passed betweenelectrodes E_(x) and E_(y). Suppose further that the load resistance Requals 800 ohms. When the current of 5 mA is passed through the loadresistance R, a voltage V_(R)=4V will build up across the resistanceload R (V=I*R). Suppose further for simplicity that the minimumdrain-to-source voltage to keep the output transistors M1 and M2 insaturation equals 1V when the effects of the selection transistors 4, 7are included. The actual value can be different, but is chosen as 1V forease of illustration. To provide this current, a minimum compliancevoltage V+ of at least 6V would be needed; if V+<6V, the circuitry willbe unable to produce the desired amount of current.

The compliance voltage V+ could be higher than 6V while still producingthe proper amount of current. For example, suppose for the same examplethat the compliance voltage V+ is 8V. In this case, the circuitry isstill capable of providing the 5 mA current, and the load (which doesn'tchange) will still drop 4V at that current. What this means is that theremainder of the compliance voltage must be dropped across the outputtransistors M1 and M2 as well as their associated selection transistors4, 7, e.g., 2V if the source and sink are matched.

However, running the circuit in this example with an 8V compliancevoltage is not efficient. While circuit performance is the same at both6V and 8V, i.e., both are capable of generating a 5 mA current. At 6V,only 30 mW of power (P=I*V) will be drawn, while at 8V, 40 mW of powerwill be drawn. In other words, 10 mW of power is needlessly droppedacross the output transistors M1, M2 and their selection transistors 4,7. This waste of power is regrettable in the context of an implantablemedical device, such as an IPG, which requires a source of energy eithersupplied by a battery or an external charging source. Therefore, it isimportant to minimize circuit operation that would otherwise needlesslydrain the battery and cause the IPG to cease functioning, or needlesslyrequire the patient to more frequency recharge the battery.

Unfortunately, it is difficult to design the compliance voltage to anoptimum level. Depending on the electrodes that are activated, themagnitude of the current required for efficient therapy for a givenpatient, and the resistance of the patient's flesh, an optimalcompliance voltage from the vantage point of power conservation isvariable. As such, mechanisms have been designed into prior artneuromodulation systems that adjust the compliance voltage each time theprogrammed electrical current amplitude or electrode combination ischanged by the user. Although the compliance voltage can theoreticallybe adjusted at a rapid rate (e.g., every minute) to compensate forpotential changes in the tissue environment, thereby ensuring that thecurrent source/sink circuitry continues to function properly to providethe current at the programmed amplitude in response to these tissueimpedance changes, the compliance voltage adjustment requires bursts ofhigh power drain, and may consume significant amounts of energy. Thus,performing too many compliance voltage adjustments will waste energy. Inextreme cases, constant compliance voltage adjustments not only createshigh system power consumption, but also prevents the IPG from performingother tasks. As such, a fixed compliance voltage margin (e.g., 12%) isbuilt into the adjusted compliance voltage to ensure that the deliveredtherapy is not compromised without having to continually make compliancevoltage adjustments.

This compliance voltage margin, of course, represents wasted energy, andif the tissue environment has stabilized over a period of time, thecompliance margin may be unnecessarily too large. Furthermore, in thecontext of some therapeutic applications, such as SCS, the change in thetissue impedance is rather slow relative to the frequency at which theamplitude and/or electrode combination, and thus the compliance voltage,is adjusted. As such, a moderate compliance voltage margin, such 12%,will be sufficient to compensate for the tissue impedance changesbetween compliance voltage adjustments.

However, in other therapeutic applications, such as DBS, it has beendiscovered that the impedance of the tissue (in the case of DBS, braintissue) varies greatly over both the long term and the short term. Inparticular, there have been a number of DBS impedance data sets fromanimal trials and limited human experiments suggesting that brain tissueimpedance tends to vary significantly during both the long term andshort term.

For example, it has been demonstrated that the tissue impedance of braintissue measured from a neuromodulation lead rapidly increases during thefirst four weeks of implantation (in this case, about 40%), graduallydecreases during the next eight weeks after implantation (in this case,about −40%), and then stabilizes thereafter, as shown in FIG. 3. If thecompliance voltage is left unchanged after implantation, the therapywill be significantly compromised (under compliance) two weeks afterimplantation until the impedance subsequently drops to a level where thecompliance voltage is sufficient. Even if the amplitude and/or electrodecombination, and thus the compliance voltage, is adjusted at least onetime during this period, thereby at least partially compensating for thechange in impedance over the long term, the compliance voltage margin,which translates to a higher compliance voltage, will be relativelylarge when the tissue impedance stabilizes, thereby unnecessarilywasting energy.

It has also been demonstrated that the tissue impedance of brain tissuemeasured from a neuromodulation lead rapidly increases from a baselinelevel to a peak during the first ten minutes of electrical energydelivery (in this case, about 30%), rapidly decreases during the nextten minutes of electrical energy delivery (in this case, about −30%),gradually decreases during the next forty minutes (in this case, about−15%), and then stabilizes thereafter, as shown in FIG. 4. Because it isunlikely that the amplitude value or electrode combination would beadjusted during the initial sixty minute period of therapy, or at leastat the rate at which compliance voltage adjustments can effectivelycompensate for the impedance changes, the therapy will be significantlycompromised during the first twenty minutes (during the rapid increaseof the tissue impedance to the peak, and the rapid decrease of thetissue impedance to the baseline level) and will considerably wasteenergy for the remainder of the therapy session (during the gradualdecrease of the tissue impedance from the baseline level).

It can be appreciated from the foregoing that an improved technique foreffectively and efficiently adjusting the compliance voltage of aneuromodulation device designed to deliver a constant current is needed.

SUMMARY OF THE INVENTION

In accordance with a first aspect of the present inventions, atherapeutic neuromodulation system is provided. The neuromodulationsystem comprises a plurality of electrical terminals configured forbeing respectively coupled to a plurality of electrodes implanted withintissue, analog output circuitry configured for delivering therapeuticelectrical energy (e.g., an electrical pulse train) between theplurality of electrical terminals in accordance with a set of modulationparameters that includes a defined current value (e.g., auser-programmed value), and a voltage regulator configured for supplyingan adjustable compliance voltage to the analog output circuitry. Theneuromodulation system optionally comprises a battery to which thevoltage regulator is coupled.

In one embodiment, the analog output circuitry comprises a currentsource and/or current sink configured for delivering the therapeuticelectrical energy between the electrical terminals. The neuromodulationsystem may further comprise a plurality of coupling capacitorsrespectively coupled to the plurality of electrical terminals, in whichcase, the current source and/or the current sink may be configured fordelivering therapeutic electrical energy between the plurality ofelectrical terminals via the capacitors.

The neuromodulation system further comprises control/processingcircuitry configured for automatically performing a compliance voltagecalibration process at a compliance voltage adjustment interval byperiodically computing an adjusted compliance voltage value as afunction of a compliance voltage margin, and directing the voltageregulator to adjust the compliance voltage to the adjusted compliancevoltage value. The compliance voltage calibration process may beperformed when the analog output circuitry delivers the therapeuticelectrical energy between the plurality of electrical terminals over acontinuous therapeutic period without changing the set of modulationparameters. The compliance voltage calibration process may be initiatedeach time the delivery of the electrical energy by the analog outputcircuitry is initiated in accordance with the unchanged set ofmodulation parameters.

The neuromodulation system may further comprise monitoring circuitryconfigured for measuring a voltage drop (e.g., across the current sourceand/or current sink, across the capacitors) in the analog outputcircuitry. In this case, the control/processing circuitry may beconfigured for computing the adjusted compliance voltage value based onthe measured voltage drop. For example, the control/processing circuitrymay be configured for computing a voltage drop across the tissue basedon a difference between the compliance voltage and the measured voltagedrop across the current source and/or current sink. Or, thecontrol/processing circuitry may be configured for computing the voltagedrop across the tissue based on a difference between the compliancevoltage and a sum of the measured voltage drop across the current sourceand/or the current sink and the measured voltage drops across thecapacitors.

In one embodiment, the control/processing circuitry may be configuredfor computing the adjusted compliance voltage value as a function of thevoltage drop across the tissue and an operating voltage of at least onecurrent source and at least one current sink. The function may be a sumof the voltage drop across the tissue, the operating voltage of at leastone current source and at least one current sink, and the compliancevoltage. In this case, the compliance voltage margin may be a percentageof the voltage drop across the tissue.

In another embodiment, the control/processing circuitry may beconfigured for directing the voltage regulator to incrementally vary thecompliance voltage to a baseline value that causes the voltage dropacross the at least one of the current source and the current sink tomeet a threshold value, and computing the adjusted compliance voltagebased on the baseline value.

In an optional embodiment, the control/processing circuitry may befurther configured for automatically adjusting the compliance voltageadjustment interval and/or compliance voltage margin during thecompliance voltage calibration process. The compliance voltageadjustment interval is typically increased over the course of thecompliance voltage calibration process. For example, the compliancevoltage adjustment interval may be adjusted from a value in the range of0-20 minutes to a value in the range greater than 20 minutes. Or, thecompliance voltage adjustment interval may be adjusted from a value inthe range of 20-60 minutes to a value in the range greater than 60minutes. Or, the compliance voltage adjustment interval may be adjustedfrom a value in the range of 60 minutes to 1 day in the range greaterthan 1 day. The compliance voltage margin, which may be a voltage droppercentage, is typically decreased over the course of the compliancevoltage calibration process. For example, the voltage drop may beadjusted from a value in the range greater than 10% to a value less than10%. Or, the voltage drop percentage may be adjusted from a value in therange between 5%-10% to a value less than 2%. Or, the voltage droppercentage may be adjusted from a value in the range of 1%-2% to a valueless than 1%.

To automatically make the adjustments to the compliance voltageadjustment intervals and/or compliance voltage margin, thecontrol/processing circuitry may be further configured for periodicallydirecting the monitoring circuitry to measure an electrical parameterdata (e.g., voltage drop across at least one component in the analogoutput circuitry) indicative of change in impedance in the tissue anddetermining voltage drops (e.g., a voltage drop across the tissue, thecompliance voltage) based on the measured electrical parameters.

The control/processing circuitry may be further configured for computinga function of at least two of the determined voltage drops and adjustingthe compliance voltage adjustment interval and/or compliance voltagemargin based on the computed function. For example, the computedfunction may be a difference in the voltage drops determined at twoconsecutive compliance voltage adjustment intervals. Or the computedfunction may be an average of voltage drop differences determinedbetween a plurality of consecutive compliance voltage adjustmentintervals. The control/processing circuitry may be further configuredfor comparing the computed function to a first threshold value, andadjusting the compliance voltage adjustment interval and/or compliancevoltage margin based on the comparison. The compliance voltageadjustment interval and/or compliance voltage margin may be adjustedonly if the computed function meets (or drops below) the first thresholdvalue.

Similar to the above, the control/processing circuitry may also beconfigured for computing another function of at least another two of thevoltage drops, and adjusting at least one of the compliance voltageinterval and the compliance voltage margin based on the other computedfunction. The other computed function may be similarly compared to asecond threshold value different from the first threshold value. Thecontrol/processing circuitry may be further configured for readjustingthe compliance voltage adjustment interval and/or compliance voltagemargin based on the other comparison. The compliance voltage adjustmentinterval and/or compliance voltage margin may be readjusted only if theother computed function meets (or drops below) the second thresholdvalue.

In an alternate embodiment, rather than dynamically adjusting thecompliance voltage adjustment interval and/or compliance voltage marginbased on periodic voltage drop measurements, the control/processingcircuitry may be configured for adjusting the at least one of compliancevoltage adjustment interval and the compliance voltage margin inaccordance with a predetermined time schedule.

The neuromodulation system may further comprise a housing containing theplurality of electrical terminals, the modulation output circuitry, thevoltage regulator, and the control/processing circuitry.

In accordance with a second aspect of the present inventions, aneuromodulation system comprises a plurality of electrical terminalsconfigured for being respectively coupled to a plurality of electrodesimplanted within tissue, analog output circuitry configured fordelivering therapeutic electrical energy between the plurality ofelectrical terminals in accordance with a set of modulation parametersthat includes a defined current value (e.g., a user-programmed value),and a voltage regulator configured for supplying an adjustablecompliance voltage to the analog output circuitry. The neuromodulationsystem further comprises control/processing circuitry configured forperforming a compliance voltage calibration process at a compliancevoltage adjustment interval by periodically computing an adjustedcompliance voltage value as a function of a compliance voltage margin,directing the voltage regulator to adjust the compliance voltage to theadjusted compliance voltage value, and for adjusting at least one of thecompliance voltage adjustment interval and the compliance voltage marginduring the voltage compliance calibration process.

The compliance voltage adjustments may be automatically performed asdescribed above or manually performed in response to user input. Theadjustment of the compliance voltage adjustment interval and/orcompliance voltage margin may be performed in the same manner describedabove.

Other and further aspects and features of the invention will be evidentfrom reading the following detailed description of the preferredembodiments, which are intended to illustrate, not limit, the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate the design and utility of preferred embodimentsof the present invention, in which similar elements are referred to bycommon reference numerals. In order to better appreciate how theabove-recited and other advantages and objects of the present inventionsare obtained, a more particular description of the present inventionsbriefly described above will be rendered by reference to specificembodiments thereof, which are illustrated in the accompanying drawings.Understanding that these drawings depict only typical embodiments of theinvention and are not therefore to be considered limiting of its scope,the invention will be described and explained with additionalspecificity and detail through the use of the accompanying drawings inwhich:

FIG. 1. is a circuit diagram of prior art current source/sink circuitryused in a therapeutic neuromodulation system for delivering current to atissue load resistance;

FIG. 2 is a plan view of current and voltage characteristics of fieldeffect transistors used in the prior art current source/sink circuitryof FIG. 1;

FIG. 3 is a plot of a typical long-term tissue impedance measured by aneuromodulation lead implanted within the brain tissue;

FIG. 4 is a plot of a typical normalized short-term impedance exhibitedby tissue measured by an active neuromodulation lead implanted withinthe brain tissue;

FIG. 5 is a plan view of a DBS system constructed in accordance with oneembodiment of the present inventions;

FIG. 6 is a profile view of an implantable pulse generator (IPG) andneuromodulation leads used in the DBS system of FIG. 5;

FIG. 7 is a plan view of the DBS system of FIG. 5 in use with a patient;

FIG. 8 is a timing diagram illustrating dynamic adjustments ofcompliance voltage margins and compliance voltage adjustment intervalsduring a compliance voltage calibration process performed by the DBSsystem of FIG. 3;

FIG. 9 is a block diagram of the internal components of the IPG of FIG.6;

FIG. 10 is a block diagram illustrating current source/sink circuitryused in the IPG of FIG. 9; and

FIG. 11a-c is a flow diagram illustrating one method performed by theIPG of FIG. 6 to periodically adjust the compliance voltage over time.

DETAILED DESCRIPTION OF THE EMBODIMENTS

The description that follows relates to a deep brain stimulation (DBS)system. However, it is to be understood that the while the inventionlends itself well to applications in DBS, the invention, in its broadestaspects, may not be so limited. Rather, the invention may be used withany type of implantable electrical circuitry used to stimulate tissue.For example, the present invention may be used as part of a pacemaker, adefibrillator, a cochlear stimulator, a retinal stimulator, a stimulatorconfigured to produce coordinated limb movement, a cortical stimulator,a spinal cord stimulator, peripheral nerve stimulator, microstimulator,or in any other neural stimulator configured to treat urinaryincontinence, sleep apnea, shoulder subluxation, headache, etc. Itshould also be appreciated that although the description of the therapyis super-threshold in that the neural tissue is stimulated, it should beappreciated that the invention also lends itself to sub-thresholdtherapy.

Turning first to FIG. 5, an exemplary DBS system 10 generally includesat least one implantable neuromodulation 12 (in this case, two), aneurostimulator in the form of an implantable pulse generator (IPG) 14,an external remote controller RC 16, a clinician's programmer (CP) 18,an External Trial Stimulator (ETS) 20, and an external charger 22.

The IPG 14 is physically connected via one or more percutaneous leadextensions 24 to the neurostimulation leads 12, which carry a pluralityof electrodes 26 arranged in an array. In the illustrated embodiment,the neurostimulation leads 12 are percutaneous leads, and to this end,the electrodes 26 may be arranged in-line along the neurostimulationleads 12. In alternative embodiments, the electrodes 26 may be arrangedin a two-dimensional pattern on a single paddle lead if, e.g., corticalbrain stimulation is desired. As will be described in further detailbelow, the IPG 14 includes pulse generation circuitry that deliverselectrical modulation energy in the form of a pulsed electrical waveform(i.e., a temporal series of electrical pulses) to the electrode array 26in accordance with a set of modulation parameters. In this case, theelectrical modulation energy is stimulation energy, and the set ofmodulation parameters is a set of stimulation parameters.

The ETS 20 may also be physically connected via the percutaneous leadextensions 28 and external cable 30 to the neurostimulation leads 12.The ETS 20, which has similar pulse generation circuitry as the IPG 14,also delivers electrical stimulation energy in the form of a pulseelectrical waveform to the electrode array 26 accordance with a set ofstimulation parameters. The major difference between the ETS 20 and theIPG 14 is that the ETS 20 is a non-implantable device that is used on atrial basis after the neurostimulation leads 12 have been implanted andprior to implantation of the IPG 14, to test the responsiveness of thestimulation that is to be provided. Thus, any functions described hereinwith respect to the IPG 14 can likewise be performed with respect to theETS 20.

The RC 16 may be used to telemetrically control the ETS 20 via abi-directional RF communications link 32. Once the IPG 14 andstimulation leads 12 are implanted, the RC 16 may be used totelemetrically control the IPG 14 via a bi-directional RF communicationslink 34. Such control allows the IPG 14 to be turned on or off and to beprogrammed with different stimulation parameter sets. The IPG 14 mayalso be operated to modify the programmed stimulation parameters toactively control the characteristics of the electrical stimulationenergy output by the IPG 14. As will be described in further detailbelow, the CP 18 provides clinician detailed stimulation parameters forprogramming the IPG 14 and ETS 20 in the operating room and in follow-upsessions.

The CP 18 may perform this function by indirectly communicating with theIPG 14 or ETS 20, through the RC 16, via an IR communications link 36.Alternatively, the CP 18 may directly communicate with the IPG 14 or ETS20 via an RF communications link (not shown). The clinician detailedstimulation parameters provided by the CP 18 are also used to programthe RC 16, so that the stimulation parameters can be subsequentlymodified by operation of the RC 16 in a stand-alone mode (i.e., withoutthe assistance of the CP 18).

The external charger 22 is a portable device used to transcutaneouslycharge the IPG 14 via an inductive link 38. Once the IPG 14 has beenprogrammed, and its power source has been charged by the externalcharger 22 or otherwise replenished, the IPG 14 may function asprogrammed without the RC 16 or CP 18 being present.

For purposes of brevity, the details of the RC 16, CP 18, ETM 20, andexternal charger 22 will not be described herein. Details of exemplaryembodiments of these devices are disclosed in U.S. Pat. No. 6,895,280,which is expressly incorporated herein by reference.

Referring to FIG. 6, the IPG 14 comprises an outer case 40 for housingthe electronic and other components (described in further detail below),and a connector 42 to which the proximal end of the neurostimulationlead 12 mates in a manner that electrically couples the electrodes 26 tothe internal electronics (described in further detail below) within theouter case 40. The outer case 40 is composed of an electricallyconductive, biocompatible material, such as titanium, and forms ahermetically sealed compartment wherein the internal electronics areprotected from the body tissue and fluids, in some cases, the outer case40 may serve as an electrode.

Each of the neurostimulation leads 12 comprises an elongated cylindricallead body 43, and the electrodes 26 take the form of ring electrodesmounted around the lead body 43. One of the neurostimulation leads 12has eight electrodes 26 (labeled E1-E8), and the other neurostimulationlead 12 has eight electrodes 26 (labeled E9-E16). The actual number andshape of leads and electrodes will, of course, vary according to theintended application. In an alternative embodiment, the electrodes 26take the form of segmented electrodes that are circumferentially andaxially disposed about the lead body 43.

Further details describing the construction and method of manufacturingpercutaneous stimulation leads are disclosed in U.S. patent applicationSer. No. 11/689,918, entitled “Lead Assembly and Method of Making Same,”and U.S. patent application Ser. No. 11/565,547, entitled “CylindricalMulti-Contact Electrode Lead for Neural Stimulation and Method of MakingSame,” the disclosures of which are expressly incorporated herein byreference.

As will be described in further detail below, the IPG 14 includes abattery and pulse generation circuitry that delivers the electricalstimulation energy in the form of a pulsed electrical waveform to theelectrode array 26 in accordance with a set of stimulation parametersprogrammed into the IPG 14. Such stimulation parameters may compriseelectrode combinations, which define the electrodes that are activatedas anodes (positive), cathodes (negative), and turned off (zero),percentage of stimulation energy assigned to each electrode(fractionalized electrode configurations), and electrical pulseparameters, which define the pulse amplitude (measured in milliamps orvolts depending on whether the IPG 14 supplies constant current orconstant voltage to the electrode array 26), pulse duration (measured inmicroseconds), pulse rate (measured in pulses per second), and burstrate (measured as the stimulation on duration X and stimulation offduration Y). The IPG 14 may be capable of delivering the stimulationenergy to the array 22 over multiple channels or over only a singlechannel.

Electrical stimulation will occur between two (or more) activatedelectrodes, one of which may be the IPG case. Simulation energy may betransmitted to the tissue in a monopolar or multipolar (e.g., bipolar,tripolar, etc.) fashion. Monopolar stimulation occurs when a selectedone of the lead electrodes 26 is activated along with the case of theIPG 14, so that stimulation energy is transmitted between the selectedelectrode 26 and case. Bipolar stimulation occurs when two of the leadelectrodes 26 are activated as anode and cathode, so that stimulationenergy is transmitted between the selected electrodes 26. Multipolarstimulation occurs when at least three of the lead electrodes 26 areactivated, e.g., two as anodes and the remaining one as a cathode, ortwo as cathodes and the remaining one as an anode.

In the illustrated embodiment, IPG 14 can individually control themagnitude of electrical current flowing through each of the electrodes.In this case, it is preferred to use current generators, whereinindividual current-regulated amplitudes from independent current sourcesfor each electrode may be selectively generated. While individuallyprogrammable electrode amplitudes are optimal to achieve fine control, asingle output source switched across electrodes may also be used,although with less fine control in programming. Further detailsdiscussing the detailed structure and function of IPGs are describedmore fully in U.S. Pat. Nos. 6,516,227 and 6,993,384, which areexpressly incorporated herein by reference.

As shown in FIG. 7, two percutaneous neurostimulation leads 12 areintroduced through a burr hole 46 (or alternatively, two respective burrholes) formed in the cranium 48 of a patient 44, and introduced into theparenchyma of the brain 49 of the patient 44 in a conventional manner,such that the electrodes 26 are adjacent a target tissue region, thestimulation of which will treat the dysfunction (e.g., the ventrolateralthalamus, internal segment of globus pallidus, substantia nigra parsreticulate, subthalamic nucleus, or external segment of globuspallidus). Thus, stimulation energy can be conveyed from the electrodes26 to the target tissue region to change the status of the dysfunction.Due to the lack of space near the location where the neurostimulationleads 12 exit the burr hole 46, the IPG 14 is generally implanted in asurgically-made pocket either in the chest, or in the abdomen. The IPG14 may, of course, also be implanted in other locations of the patient'sbody. The lead extension(s) 24 facilitates locating the IPG 14 away fromthe exit point of the neurostimulation leads 12.

More significant to the present inventions, because the patienttypically does not feel paresthesia during DBS therapy, the user may notnotice an interruption in DBS therapy if the IPG 14 stops functioningdue to the highly variable nature of brain tissue impedance. Thus, toensure that the IPG 14 functions smoothly with sufficient compliancevoltage to compensate for the varying tissue impedance, the DBS system10 (shown in FIG. 5) is configured for automatically making periodicadjustments to the compliance voltage, such that efficacious tissueneuromodulation is maintained without unnecessarily wasting energy. Thatis, after a compliance voltage calibration process is initiated by theuser, the periodic adjustments to the compliance voltage are madewithout any user intervention.

The compliance voltage calibration process entails making periodicautomatic compliance voltage adjustments until the IPG 14 is turned offor a new compliance voltage calibration process is initiated. Thecompliance voltage calibration process is initiated when electricalenergy associated with a set of modulation parameters is delivered tothe tissue, and re-initiated whenever there is a change in the set ofmodulation parameters (e.g., amplitude, pulse width, pulse rate)associated with the delivered electrical energy. In other words, thecompliance voltage calibration process is initiated whenever electricalenergy having a new set of modulation parameters (e.g., whenever the IPGis turned on or whenever there is a change in the set of modulationparameters) is delivered to the tissue.

The DBS system 10 is configured for making the periodic automaticcompliance voltage adjustments at compliance voltage adjustmentintervals. The compliance voltage adjustment interval is the period oftime between two consecutive compliance voltage adjustments. After eachcompliance voltage adjustment interval, the DBS system 10 is configuredfor computing an adjusted compliance voltage as a function of acompliance voltage margin. The compliance voltage margin compensates forany drastic changes in tissue impedance, on top of a baseline compliancevoltage necessary to deliver the programmed electrical current to thetissue. At each compliance voltage adjustment, the DBS system 10 isconfigured for incorporating an appropriate computed compliance voltagemargin into the adjusted compliance voltage in a manner that, prior tothe next compliance voltage adjustment, compensates for the varyingtissue impedance in the short-term (as shown in FIG. 4) and thelong-term (as shown in FIG. 3).

In one embodiment, the compliance voltage margin may be a percentage ofone or more voltage drops generated by the IPG 14. For example, in thepreferred embodiment, the compliance voltage margin may be a percentageof tissue voltage drop V_(R) across the tissue resistance R (shown inFIG. 1). In another example, the compliance voltage margin may be apercentage of the voltage drop across certain components of the analogoutput circuitry (described in further detail below with respect to FIG.11.). Ostensibly, since the tissue voltage drop V_(R) changes mostdramatically as a result of the varying impedance exhibited by thetissue, calculating the compliance voltage margin as a percentage ofV_(R) may prove most efficient. In another embodiment, the compliancevoltage margin may simply be a fixed voltage margin.

Significantly, the DBS system 10 is configured to adjust both thecompliance voltage margin and the compliance voltage adjustment intervalto mirror the underlying changes in tissue impedance while minimizingunnecessary power consumption.

In particular, the DBS system 10 is configured for maintaining arelatively high compliance voltage margin (e.g., 10%), during a firstperiod when the tissue impedance is rapidly fluctuating in theshort-term (e.g., the first 20 minutes after the start of tissuemodulation in FIG. 4), maintaining a relatively moderate compliancevoltage margin (e.g., 5%), during a second period when the tissueimpedance is changing at a decreased rate in the short-term (e.g., thenext 40 minutes in FIG. 4), and maintaining a relatively low compliancevoltage margin (e.g., 2% or 3%), during a third period when the tissueimpedance is changing at an even more decreased rate in the short-term(e.g., after an hour in FIG. 4); that is, when the tissue impedance hasstabilized.

In a similar vein, the DBS system 10 is configured for maintaining arelatively short compliance voltage adjustment interval (e.g., 1minute), at which the voltage compliance adjustments are made during thefirst period when the tissue impedance is rapidly fluctuating in theshort-term (e.g., the first 20 minutes after the start of tissuemodulation in FIG. 4), maintaining a relatively moderate compliancevoltage adjustment interval (e.g., 5 minutes), at which the voltagecompliance adjustments are made during the second period when the tissueimpedance is changing at a decreased rate in the short-term (e.g., thenext 40 minutes in FIG. 4), and maintaining a relatively long compliancevoltage adjustment interval (e.g., 4 hours or 24 hours), at which thevoltage compliance adjustments are made during the third period when thetissue impedance is changing at an even more decreased rate in theshort-term (e.g., after an hour in FIG. 4); that is, when the tissueimpedance has stabilized.

It should be appreciated that the DBS system 10 is further configuredfor adjusting the compliance voltage margin and the compliance voltageadjustment interval to compensate for long-term trends in tissueimpedance in addition to the short-term trends in tissue impedancediscussed above. In the first 4 weeks after implantation, the tissueimpedance is still increasing (as shown in FIG. 3), albeit at a muchslower rate when compared to the rapid increase in tissue impedanceobserved during the first 10 minutes of delivering electrical energy (asshown in FIG. 4). After the first 4 weeks, the tissue impedance steadilydecreases until week 15 after which the tissue impedance is mostlystable. While the long-term changes in tissue impedance (as shown inFIG. 3) only occur in the few months immediately after implantation, theshort-term changes in tissue impedance resulting from the cycling of theIPG 14 on or the adjustment in the modulation parameters (as shown inFIG. 4) are much more drastic than the long-term changes in tissueimpedance. Thus, the DBS system 10 essentially compensates forshort-term tissue impedance changes over the course of the first andsecond periods. However, the long-term changes in tissue impedance maybe greater than the stabilized short-term tissue impedance during thethird period, and thus, the compliance voltage margin and/or thecompliance voltage adjustment may be adjusted differently at the thirdperiod based on when (in the course of time after implantation) thecompliance voltage calibration process is initiated.

In particular, during the third period, after the short-term impedancehas stabilized, the DBS system 10 is configured for maintaining arelatively low compliance voltage margin (e.g., 3%), when the long-termimpedance has not yet completely stabilized (e.g., the first 4 weeksafter implantation in FIG. 3) and maintaining a minimally low compliancevoltage margin (e.g., 2%), when the long-term impedance is decreasingslowly or has stabilized (e.g., after the first 4 weeks in FIG. 3).Similarly, during the third period, after the short-term impedance hasstabilized, the DBS system 10 is configured for maintaining relativelylong compliance voltage adjustment intervals (e.g., 4 hours), when thelong-term impedance has not yet completely stabilized (e.g., the first 4weeks after implantation in FIG. 3) and maintaining very long compliancevoltage adjustment intervals (e.g., 24 hours), during the third periodwhen the long-term impedance is decreasing slowly or has stabilized(e.g., after the first 4 weeks in FIG. 3).

It should be appreciated that adjustments made to the compliance voltagemargins and/or compliance voltage adjustment intervals in the first andsecond periods will be identical regardless of whether the tissueexhibits long-term impedance or not. Since long-term impedance changes,relative to the short-term impedance changes, are slow, and occur over along period of time, its effects are only reflected in adjustments madeto the compliance voltage margin and/or compliance voltage adjustmentintervals in the third period after the effects of the rapidlyfluctuating short-term impedance have subsided. Exemplary techniques ofadjusting the compliance voltage margin and/or compliance voltageadjustment interval will be discussed below.

In the preferred embodiment, the DBS system 10 dynamically adjusts thecompliance voltage margin and/or the compliance voltage adjustmentinterval based on electrical parameter data indicative of tissueimpedance that is measured at compliance voltage adjustment intervals.Measuring electrical parameter data related to tissue impedance allows ameans for tracking a change in tissue impedance at every compliancevoltage adjustment interval, such that the compliance voltage marginand/or compliance voltage adjustment interval may be adjusted to bettersuit a current and known state of tissue impedance change. This allowsfor precise and efficient compliance voltage adjustments such that thecompliance voltage margin is only decreased and/or the compliancevoltage adjustment interval is only increased at a point when themeasured data indicates that a change in tissue impedance hassufficiently decreased and not any sooner than that point.

In the illustrated embodiment, the electrical parameter data that ismeasured by the DBS system 10 is the tissue voltage drop V_(R). Althoughother voltage drops across certain components of the IPG 14 may besimilarly used, as will be discussed in further detail below, the tissuevoltage drop V_(R) is the preferred electrical parameter data sincechanges in the tissue voltage drop V_(R) best mirror the changes intissue impedance, as discussed previously. Thus, for ease ofillustration, the following discussion will focus on the tissue voltagedrop V_(R).

To determine how fast the tissue impedance is changing, the DBS system10 is configured for computing a function of the tissue voltage dropsV_(R) measured at multiple compliance voltage adjustment intervals. Inone embodiment, the computed function of the tissue voltage drops V_(R)may be a difference in the tissue voltage drops V_(R) measured atmultiple compliance voltage adjustment intervals. The difference may becalculated between tissue voltage drops V_(R) measured at consecutivecompliance voltage adjustment intervals. For example, to determine theshort-term rate of impedance change during the first hour of thecompliance voltage calibration process, the DBS system 10 may calculatea difference in consecutive tissue voltage drops V_(R) measured at everycompliance voltage adjustment interval (e.g., 1 minute intervals duringthe first period or 5 minute intervals during the second period). Or thedifference may be calculated between tissue voltage drops V_(R) at anytwo specific compliance voltage adjustment intervals. For example, todetermine the long-term rate of impedance change, the DBS system 10 maycalculate a difference in tissue voltage drops V_(R) at 24 hourintervals thereby tracking a daily change in impedance starting at thepoint of implantation.

In another embodiment, the computed function may be an average of thedifferences of measured tissue voltage drop V_(R) at multiple compliancevoltage adjustment intervals. Using an average of the differencesbetween the tissue voltage drops V_(R) at consecutive compliance voltageadjustment intervals (e.g., the most recent intervals) may eliminateoutlier measurements, and prove to be a more reliable indicator of thechange in impedance than using individual difference values. Forexample, to determine the short-term rate of impedance change during thefirst hour of the compliance voltage calibration process, the DBS system10 may calculate art average of the three most recent differencesbetween consecutively measured tissue voltage drops V_(R). Similarly, todetermine the long-term rate of impedance change to be used in makingcompliance voltage adjustments during the third period, the DBS system10 may calculate at average of the three most recent daily-measureddifferences of the tissue voltage drops V_(R).

The computed function of the multiple tissue voltage drops V_(R)(measured at multiple compliance voltage adjustment intervals) iscompared to a set of threshold values, each of which is indicative of arate of impedance change that corresponds to a suitable compliancevoltage margin and/or compliance voltage adjustment interval. Typically,the set of threshold values is in descending order such that the largestthreshold value represents a more rapidly changing tissue impedance, andthe smallest threshold value represents a stable tissue impedance. Itshould be appreciated that there may be separate threshold valuesindicative of short-term rates of impedance change and long-term ratesof impedance change. Thus, the computed function of the tissue voltagedrops V_(R) measured at short consecutive compliance voltage adjustmentintervals (short-term tissue voltage drops V_(R)) may be compared to theshort-term set of threshold values indicative of short-term rates ofimpedance change to accordingly adjust the compliance voltage marginand/or compliance voltage adjustment interval for the first two periodsof the compliance voltage calibration process. Once the short-termimpedance has stabilized, the computed function of the tissue voltagedrops V_(R) measured daily (long-term tissue voltage drops V_(R)) may becompared to a long-term threshold value indicative of long-term stableimpedance to accordingly adjust the compliance voltage margin and/orcompliance voltage adjustment interval during the third period of thecompliance voltage calibration process.

When the computed function of the tissue voltage drops V_(R) becomesequal to or drops below one of the threshold values, the DBS system 10automatically adjusts the compliance voltage margin and/or compliancevoltage adjustment interval corresponding to that threshold value. Thecompliance voltage margin and/or compliance voltage adjustment intervalat following compliance voltage adjustment intervals will be maintainedat this adjusted compliance voltage margin and/or this adjustedcompliance voltage adjustment interval until the computed function meetsor falls below another threshold value that is indicative of more stableimpedance.

Although not illustrated in FIG. 3, it should be appreciated that evenafter tissue impedance has stabilized in the months after implantation,it may increase or decrease or generally become unstable at a later timedue to unforeseen circumstances (e.g., a change in position of theneuromodulation leads 12, an unforeseen change in brain tissue, etc.).In such a case, the long-term impedance curve shown in FIG. 3 may repeatitself at the later time such that the compliance voltage margin and/orcompliance voltage adjustment interval are once again adjusteddifferently during the third period based on when (over the course ofthe new long-term impedance change) the compliance voltage calibrationprocess is initiated. Thus, as a result of the increasing long-termimpedance, if the computed function of the long-term tissue voltagedrops V_(R) becomes greater than the long-term threshold valueindicative of stable impedance, the DBS system 10 accordingly adjuststhe compliance voltage margin and/or compliance voltage adjustmentinterval to those appropriate for long-term unstable impedance.

Referring now to FIG. 8, one exemplary embodiment of dynamicallyadjusting both the compliance voltage margin and the compliance voltageadjustment interval based on both short-term and long-term tissuevoltage drops V_(R) is illustrated. During Period 1 of the compliancevoltage calibration process (compliance voltage margin adjustments of10% made at compliance voltage adjustment intervals of 1 minute), thedifference between short-term tissue voltage drops V_(R) is greater thanShort-term Threshold Value 1. When the difference between short-termtissue voltage drops V_(R) meets or drops below Short-term ThresholdValue 1, the DBS system 10 automatically switches from Period 1 toPeriod 2. During Period 2 (compliance voltage margin adjustments of 5%made at compliance voltage adjustment intervals of 5 minutes), thedifference between short-term tissue voltage drops V_(R) remains equalto or less than Short-term Threshold Value 1, but greater thanShort-term Threshold Value 2. When the difference between short-termtissue voltage drops V_(R) meets or drops below Short-term ThresholdValue 2, the DBS system 10 switches from Period 2 to either Period 3 aor Period 3 b based on long-term stability of tissue impedance.

In particular, when the difference between the short-term tissue voltagedrops V_(R) meets or drops below Short-term Threshold Value 2, but thedifference between long-term tissue voltage drops V_(R) is greater thanLong-term Threshold Value 1, the DBS system 10 automatically switchesfrom Period 2 to Period 3 a. During Period 3 a (compliance voltagemargin adjustments of 3% made at compliance voltage adjustment intervalsof 4 hours), the difference between the short-term tissue voltage dropsV_(R) remains equal to or less than Short-term Threshold Value 2, andthe difference between long-term tissue voltage drops V_(R) remainsgreater than Long-term Threshold Value 1.

In contrast, when the difference between the short-term tissue voltagedrops V_(R) meets or drops below Short-term Threshold Value 2, and thedifference between long-term tissue voltage drops V_(R) meets or dropsbelow Long-term Threshold Value 1, the DBS system 10 automaticallyswitches from Period 2 to Period 3 b. During Period 3 b (compliancevoltage margin adjustments of 2% made at compliance voltage adjustmentintervals of 24 hours), the difference between the short-term tissuevoltage drops V_(R) remains equal to or less than Short-term ThresholdValue 2, and the difference between long-term tissue voltage drops V_(R)remains equal to or less than Long-term Threshold Value 1.

In an alternate embodiment, instead of dynamically adjusting thecompliance voltage margin and/or the compliance voltage adjustmentintervals based on electrical parameter data measured at priorcompliance voltage adjustments, the compliance voltage margin and/orcompliance voltage adjustment intervals may be automatically adjustedbased on a predetermined time schedule. The predetermined time schedulemay be designed based on empirical studies performed on previouspatients. Although this embodiment may not follow tissue impedance asclosely as the preferred embodiment does, as described above, it may bemore energy-efficient because energy is not used in measuring electricalparameter data to determine when to adjust the compliance voltage marginand/or compliance voltage adjustment interval.

For example, still referring to FIG. 8, to compensate for short-termimpedance, instead of requiring the difference in tissue voltage dropsV_(R) to reach a particular threshold value before switching periods,the DBS system 10 may automatically switch from Period 1 to Period 2after the first 20 minutes of the compliance voltage calibrationprocess. After another 40 minutes have elapsed, the DBS system 10 maythen automatically switch from Period 2 to either Period 3 a or Period 3b depending on when the neuromodulation leads 12 were implanted into thetissue.

To compensate for long-term impedance during the third period, after theshort-term impedance has stabilized, instead of tracking the dailychange of impedance to determine whether the long-term impedance hasstabilized, the DBS system 10 may automatically adjust the compliancevoltage margin and/or the compliance voltage adjustment intervaldifferently after a predetermined time (e.g., 5 weeks) afterimplantation has elapsed. For example, at compliance voltage calibrationprocesses initiated during the first five weeks after implantation, theDBS system 10 may automatically switch from Period 2 to Period 3 a afterthe 40 minutes of Period 2 have elapsed. Period 3 a is then maintaineduntil the IPG is turned off or a new compliance voltage calibrationprocess is initiated. Similarly, at compliance voltage calibrationprocesses initiated any time after the first five weeks of implantation,the DBS system 10 may automatically switch from Period 2 to Period 3 bafter the 40 minutes of Period 2 have elapsed. Period 3 b is similarlymaintained until the IPG is turned off or a new compliance voltagecalibration process is initiated. It should be appreciated that thepredetermined time schedule may be programmed by the user and may bemodified to better suit the long-term and short-term changes in tissueimpedance.

Although the compliance voltage margin and compliance voltage adjustmentinterval are illustrated as being adjusted together in the foregoingexample, it should be appreciated that the compliance voltage margin andthe compliance voltage interval may be adjusted independently of theother. For example, if the compliance voltage calibration process isinitiated when the tissue impedance is declining steadily but has notstabilized completely (e.g., week 4-15 in FIG. 3), the compliancevoltage margin may be decreased from 3% to 2%, but the compliancevoltage adjustment interval may remain at 4 hours. Or, in anotherexample, when the tissue impedance is declining steadily during thesecond period of the compliance voltage calibration process (e.g.,minutes 20-60 in FIG. 4), the compliance voltage margin may be decreasedfrom 5% to 3%, but the compliance voltage adjustment interval may remainat 5 minutes.

Turning next to FIG. 9, the main internal components of the IPG 14 willnow be described. The IPG 14 includes analog output circuitry 50configured for generating electrical stimulation energy in accordancewith a defined pulsed waveform having a specified pulse amplitude, pulserate, pulse duration, and pulse shape under control of control logic 52over data bus 54. Control of the pulse rate and pulse duration of theelectrical waveform is facilitated by timer logic circuitry 56, whichmay have a suitable resolution, e.g., 10 μs. The electrical stimulationenergy generated by the analog output circuitry 50 is output toelectrical terminals 58 corresponding to electrodes E1-E16 and E_(case).

The analog output circuitry 50 may either comprise one or moreindependently controlled electrical sources, which take the form ofcurrent sources and/or current sinks, for providing stimulation pulsesof a specified and known amperage to or from the electrodes 26, orvoltage sources and/or voltage sinks for providing stimulation pulses ofa specified and known voltage at the electrodes 26. The current (orvoltage) sources or sinks include constant current (or voltage) sourcesand associated analog switches to generate the electrical pulse trains.

For example, in the illustrated embodiment, the analog output circuitry50 comprises a plurality m independent current source/sink pairs 60conveying electrical stimulation energy between the electrical terminals58 at a specified and known amperage. Each pair 60 includes a currentsource 62 that functions as a positive (+) or anodic current source(e.g., a PDAC), and a current sink 64 that functions as a negative (−)or cathodic current sink (e.g., an NDAC). The outputs of the anodiccurrent source 62 and the cathodic current sink 64 of each pair 60 areconnected to a common node 66.

In essence, each current source/sink pair 60 takes the form of areconfigurable current source whose polarity can be switched. That is,by activating the anodic current source 62 and deactivating the cathodiccurrent sink 64, the current source/sink pair 60 can be configured as ananodic current source, and by deactivating the anodic current source 62and activating the cathodic current sink 64, the current source/sinkpair 60 can be configured as a cathodic current sink. The current source62 and current sink 64 may, e.g., take the form of the current source 1and current sink 2 illustrated in FIG. 1.

The analog output circuitry 50 further comprises a low impedanceswitching matrix 68 through which the common node 66 of each currentsource/sink pair 60 is connected to any of the electrical terminals 58,and a capacitor 70 coupled between each electrode 26 and the switchingmatrix 68. Thus, for example, it is possible to program the first anodiccurrent source 62 (+I1) to produce a pulse having a peak amplitude of +4mA (at a specified rate and for a specified duration), and tosynchronously program the second cathodic current sink 64 (−I2) tosimilarly produce a pulse having a peak amplitude of −4 mA (at the samerate and pulse duration), and then connect the node 66 of the anodiccurrent source 62 (+I1) to the electrical terminal 68 corresponding toelectrode E3, and connect the node 66 of the cathodic current sink 64(−I2) to the electrical terminal 68 corresponding to electrode E1.

Hence, it is seen that each of the programmable electrical terminals 58can be programmed to have a positive (sourcing current), a negative((sinking current), or off (no current) polarity. Further, the amplitudeof the current pulse being sourced or sunk to or from a given electrodemay be programmed to one of several discrete current levels, e.g.,between 0 to 10 mA in steps of 100 μA, within the output voltage/currentrequirements of the IPG 14. Additionally, in one embodiment, the totalcurrent output by a group of electrical terminals 58 can be up to ±20 mA(distributed among the electrodes included in the group). Also, thepulse duration of the current pulses is preferably adjustable inconvenient increments, e.g., from 0 to 1 milliseconds (ms) in incrementsof 10 microseconds (μs). Similarly, the pulse rate is preferablyadjustable within acceptable limits, e.g., from 0 to 5000 pulses persecond (pps). Other programmable features can include slow start/endramping, burst stimulation cycling (on for X time, off for Y time),interphase (i.e., the duration between first and second phases ofbiphasic energy), and open or closed loop sensing modes. Moreover, it isseen that each of the electrical terminals 58 can operate in amultipolar mode, e.g., where two or more electrical terminals aregrouped to source/sink current at the same time. Alternatively, each ofthe electrical terminals 58 can operate in a monopolar mode where, e.g.,the electrical terminals 58 are configured as cathodes (negative), andcase of the IPG 14 is configured as an anode (positive).

It can be appreciated that an electrical terminal 58 may be assigned anamplitude and included with any of up to k possible groups, where k isan integer corresponding to the number of channels, and in oneembodiment, is equal to 4, and with each channel k having a definedpulse amplitude, pulse duration, pulse rate, and pulse shape. Otherchannels may be realized in a similar manner. Thus, each channelidentifies which electrical terminals 58 (and thus electrodes) areselected to synchronously source or sink current, the pulse amplitude ateach of these electrical terminals, and the pulse duration, pulse rate,and pulse shape. The individual electrical pulse trains that areconcurrently generated to create the combined electrical pulse train canbe respectively conveyed in the k number of channels. Amplitudes andpolarities of electrodes on a channel may vary, e.g., as controlled bythe RC 16. External programming software in the CP 18 is typically usedto set stimulation parameters including electrode polarity, amplitude,pulse rate and pulse duration for the electrodes of a given channel,among other possible programmable features.

Further details discussing this type of current source architecture isdescribed in U.S. Pat. No. 6,181,996, which has previously beenincorporated by reference. Of course, other types of current sourcearchitectures, such as the dedicated current source architecturedescribed in U.S. Pat. No. 6,516,227 or the distributed current sourcearchitecture described in U.S. patent application Ser. No. 11/177,503,which have been previously incorporated herein by reference, canalternatively be used.

The IPG 14 further comprises monitoring circuitry 72 for monitoring thestatus of various nodes or other points 74 throughout the IPG 14, e.g.,power supply voltages, temperature, battery voltage, and the like.Notably, the electrodes 26 fit snugly within the epidural space of thespinal column, and because the tissue is conductive, electricalmeasurements can be taken between the electrodes 26. Thus, themonitoring circuitry 72 is configured for taking such electricalmeasurements (e.g., current output magnitude, electrode impedance, fieldpotential, evoked action potentials, etc.) for performing such functionsas detecting fault conditions between the electrodes 26 and the analogoutput circuitry 50, determining the coupling efficiency between theelectrodes 26 and the tissue, facilitating lead migration detection,etc. More significant to the present inventions, the monitoringcircuitry 72 is configured for measuring voltage drops across all of thecurrent sources 62, current sinks 64, and capacitors C1-C16.

The IPG 14 further comprises processing circuitry in the form of amicrocontroller (μC) 76 that controls the control logic over data bus78, and obtains status data from the monitoring circuitry 72 via databus 80. The IPG 14 additionally controls the timer logic 56 andswitching matrix 68. The IPG 14 further comprises memory 82 andoscillator and clock circuitry 84 coupled to the microcontroller 76. Themicrocontroller 76, in combination with the memory 82 and oscillator andclock circuit 84, thus comprise a microprocessor system that carries outa program function in accordance with a suitable program stored in thememory 82. Alternatively, for some applications, the function providedby the microprocessor system may be carried out by a suitable statemachine. The memory 82 also stores the threshold values, and optionallythe compliance voltage adjustment time schedule, discussed above withrespect to the adjustment of the compliance voltage adjustment intervaland compliance voltage margin.

Thus, the microcontroller 76 generates the necessary control and statussignals, which allow the microcontroller 76 to control the operation ofthe IPG 14 in accordance with a selected operating program andstimulation parameters. In controlling the operation of the IPG 14, themicrocontroller 76 is able to individually generate the individualelectrical pulse trains at the electrodes 26 using the analog outputcircuitry 50, in combination with the control logic 52 and timer logic56, thereby activating selected ones of the electrodes 26, including themonopolar case electrode. In accordance with stimulation parametersstored within the memory 82, the microcontroller 76 may control thepolarity, amplitude, rate, pulse duration and channel through which thecurrent stimulation pulses are provided. The microcontroller 76 alsofacilitates the storage of electrical parameter data (or other parameterdata) measured by the monitoring circuitry 72 within memory 82, and alsoprovides any computational capability needed to analyze the rawelectrical parameter data obtained from the monitoring circuitry 72 andcompute numerical values from such raw electrical parameter data. Moresignificant to the present inventions, the microcontroller 76 is capableof adjusting the compliance voltage supplied to the analog outputcircuitry 50 in accordance with the compliance voltage calibrationdiscussed above.

The IPG 14 further comprises an alternating current (AC) receiving coil86 for receiving programming data (e.g., the operating program and/orstimulation parameters) from the RC 16 and/or CP 18 (shown in FIG. 5) inan appropriate modulated carrier signal, and charging and forwardtelemetry circuitry 88 for demodulating the carrier signal it receivesthrough the AC receiving coil 86 to recover the programming data, whichprogramming data is then stored within the memory 82, or within othermemory elements (not shown) distributed throughout the IPG 14.

The IPG 14 further comprises back telemetry circuitry 90 and analternating current (AC) transmission coil 92 for sending informationaldata sensed through the monitoring circuitry 72 to the RC 16 and/or CP18. The back telemetry features of the IPG 14 also allow its status tobe checked. For example, when the RC 16 and/or CP 18 initiates aprogramming session with the IPG 14, the capacity of the battery istelemetered, so that the external programmer can calculate the estimatedtime to recharge. Any changes made to the current stimulus parametersare confirmed through back telemetry, thereby assuring that such changeshave been correctly received and implemented within the implant system.Moreover, upon interrogation by the RC 16 and/or CP 18, all programmablesettings stored within the IPG 14 may be uploaded to the RC 16 and/or CP18. The back telemetry features allow raw or processed electricalparameter data (or other parameter data) previously stored in the memory82 to be downloaded from the IPG 14 to the RC 16 and/or CP 18.

The IPG 14 further comprises a rechargeable power source 94 and powercircuits 96 for providing the operating power to the IPG 14. Therechargeable power source 94 may, e.g., comprise a lithium-ion orlithium-ion polymer battery. The rechargeable battery 94 provides anunregulated voltage to the power circuits 96. The power circuits 96, inturn, generate the various voltages 98, some of which are regulated andsome of which are not, as needed by the various circuits located withinthe IPG 14. Significantly, the power circuits 96 include a voltageregulator (discussed in further detail below) that supplies thecompliance voltage to the analog output circuitry 50. The rechargeablepower source 94 is recharged using rectified AC power (or DC powerconverted from AC power through other means, e.g., efficient AC-to-DCconverter circuits, also known as “inverter circuits”) received by theAC receiving coil 86. To recharge the power source 94, the externalcharger 22 (shown in FIG. 1), which generates the AC magnetic field, isplaced against, or otherwise adjacent, to the patient's skin over theimplanted IPG 14. The AC magnetic field emitted by the external chargerinduces AC currents in the AC receiving coil 86. The charging andforward telemetry circuitry 88 rectifies the AC current to produce DCcurrent, which is used to charge the power source 94. While the ACreceiving coil 86 is described as being used for both wirelesslyreceiving communications (e.g., programming and control data) andcharging energy from the external device, it should be appreciated thatthe AC receiving coil 86 can be arranged as a dedicated charging coil,while another coil can be used for bi-directional telemetry.

It should be noted that the diagram of FIG. 9 is functional only, and isnot intended to be limiting. Those of skill in the art, given thedescriptions presented herein, should be able to readily fashionnumerous types of IPG circuits, or equivalent circuits, that carry outthe functions indicated and described, which functions include not onlyproducing a stimulus current or voltage on selected groups ofelectrodes, but also the ability to measure electrical parameter data atan activated or non-activated electrode.

Additional details concerning the above-described and other IPGs may befound in U.S. Pat. No. 6,516,227, U.S. Patent Publication No,2003/0139781, and U.S. patent application Ser. No. 11/138,632, entitled“Low Power Loss Current Digital-to-Analog Converter Used in anImplantable Pulse Source,” which are expressly incorporated herein byreference. It should be noted that rather than an IPG, the SCM system 10may alternatively utilize an implantable receiver-stimulator (not shown)connected to leads 12. In this case, the power source, e.g., a battery,for powering the implanted receiver, as well as control circuitry tocommand the receiver-stimulator, will be contained in an externalcontroller inductively coupled to the receiver-stimulator via anelectromagnetic link. Data/power signals are transcutaneously coupledfrom a cable-connected transmission coil placed over the implantedreceiver-stimulator. The implanted receiver-stimulator receives thesignal and generates the stimulation in accordance with the controlsignals.

With the basic architecture of the IPG 14 understood, the specificcircuitry involved with adjusting the compliance voltage V+ supplied tothe analog output circuitry 50 will now be discussed with reference toFIG. 10. As there shown, a circuit is created that includes thecompliance voltage V+, a current source 62, a current sink 64, anelectrode or electrodes E_(x), capacitor(s) C_(x) corresponding to theelectrode(s) E_(x), an electrode or electrodes E_(y), capacitor(s) C_(y)corresponding to the electrode(s) E_(y), and the load resistance of thetissue R_(x). Due to the flow of the electrical current I_(out), voltagedrops V_(x) and V_(cy) will be respectively generated across the currentsource 62 and the coupling capacitor(s) C_(x). Similarly, due to theflow of the electrical current I_(in), voltage drops V_(y) and V_(cy)will be respectively generated across the current sink 64 and thecoupling capacitor(s) C_(y). Due to the flow of the electrical currentsI_(out), I_(in), in combination with any currents generated by otheractive current sources 62/sinks 64, a voltage drop V_(R) is generatedacross the tissue resistance R. Of course, if only one current source 62and only one current sink 64 are active, I_(out) will be equal toI_(in), and therefore, the entire voltage drop V_(R) across the tissueresistance R will be caused by the electrical current I_(out)/I_(in).

As noted earlier, the compliance voltage V+ can be set to various valueswhile still exhibiting satisfactory current sourcing/sinkingperformance. Thus, the current sources involved in stimulation of tissuecan be powered by a compliance voltage V+ ranging from a minimum value(below which current will be too low) to any maximum value that thevoltage regulator of the power circuits 96 is capable of providing.Within this range, the stimulation current desired by a particulartherapeutic regimen can be provided. However, as previously discussed,while the compliance voltage V+ can vary over a range of values whileexhibiting satisfactory voltage, power is needlessly lost should thecompliance voltage V+ be set to a value that is too high.

To this end, the monitoring circuitry 72 measures the voltage across (atleast) the output of the current sources 62 and current sinks 64involved in sinking and sourcing the electrical stimulation current. Inthe illustrated embodiment, the monitoring circuitry 72 comprises acompliance voltage sensing control circuitry 102, a switching matrix104, and at least one voltage sensor 106. Lines 108 associated with theelectrodes 26 feed into the switching matrix 104. In the givenarchitecture illustrated in FIG. 10, more than one current source 62 ormore than one current sink 64 may contribute to the current at aparticular electrode. However, for ease of illustration, only onecurrent source 60 and only one current sink 62 are shown and described.

Given their tap points, the voltage present on the lines 108 isindicative of the output voltage of the current source 60 and currentsink 64, and can thus, be used to sense the output voltage of thesecomponents. The output voltage across the current source 62 at electrodeor electrode E_(x) equals the difference between the compliance voltageV+ measured at line L_(V+) and the voltage measured at line L_(x). Theoutput voltage across the current sink 64 at electrode E_(y) equals thedifference between the voltage measured at line L_(y) and the voltagemeasured at ground L_(GND). The voltages on the lines 108 are providedto the switching matrix 104. As noted above, while only four lines 108are shown for each of illustration in FIG. 10, many more lines would bepresent, depending on the number of electrodes 26 present. The switchingmatrix 104 is used to select the voltage on one line 108 and present itto the voltage sensor 106 as either L₁ or L₂ or select two voltage ontwo lines 108 and present them to the voltage sensor 106 as L₁ and L₂for difference voltage calculations by the voltage sensor 106. As can beseen, the current source 62, current sink 64, switching matrix 104, andvoltage sensor 106 are all controlled by the compliance voltage sensingcontrol circuitry 102 via busses 112, 114, and 116.

Ultimately, the compliance voltage sensing circuitry 102 receivescontrol signals from the microcontroller 76, which informs themonitoring circuitry 72 when and how the various measurements are to bemade consistent with the compliance voltage adjustment calibrationprocess described above. The voltage sensor 106 outputs an analog outputvoltage “Out” to the microcontroller 76, which contains ananalog-to-digital (A/D) interface 110. This allows the microcontroller76 to understand and digitally process the output voltage Out todetermine the sensed voltage drops across the current source 62 orcurrent sink 64.

Further details discussing the monitoring circuitry 72 illustrated inFIG. 10 are discussed in U.S. Pat. No. 8,175,719, which is expresslyincorporated herein by reference. Based on the baseline compliancevoltages determined over a period of time, the microcontroller 76 mayadjust the compliance voltage, compliance voltage margin, and/orcompliance voltage sensing interval in the manner described above.

With knowledge of these sensed voltages, the microcontroller 76 may sendcontrol signals to a voltage regulator 118 (i.e., the circuitry thatultimately adjusts the compliance voltage V+) in accordance with thecompliance voltage adjustment calibration process.

In the illustrated embodiment, the microcontroller 76 computes theadjusted compliance voltage based on a voltage drop across the tissuebetween the electrode(s) E_(x) associated with selected one of thecurrent sources 62 and the electrode(s) E_(y) associated with a selectedone of the current sinks 64. Preferably, the current source 62 andcurrent sink 64 that are selected are the worst-case current source 62and current sink 64 (i.e., the active current source 62 with the lowestvoltage drop relative to the other active current sources 62, and theactive current sink 64 with the lowest voltage drop relative to theother active current sinks 64). As such, it can be ensured that theadjusted compliance voltage will be sufficient for all of the currentsources 62/current sinks 64.

The microcontroller 76 can determine the voltage drop V_(R) across thetissue resistance R by computing the difference between the knowncompliance voltage V+ and the sum of the measured voltage drops V_(x),V_(y) across the current source 62 and current sink 64 and the knownvoltage drops V_(cx), V_(cy), across the coupling capacitors C_(x),C_(y) (which can be obtained using Ohms' Law from the known currentsI_(out), I_(in) and the values of the capacitors C_(x), C_(y)). That is,V_(R)=V+−(V_(x)+V_(y)+V_(cx)+V_(cy)). Knowing the voltage drop V_(R)across the tissue resistance R, the microcontroller 76 can then computethe adjusted compliance voltage as a function of the voltage drop V_(R)across tissue resistance R, the desired operating voltages of thecurrent source 62 and current sink 64, the expected voltage dropsV_(cx), V_(cy) across the coupling capacitors C_(x), C_(y), and thecompliance voltage margin.

If the compliance voltage margin takes the form of a percentage,microcontroller 76 can apply the compliance voltage margin to thevoltage drop V_(R) across the tissue resistance R by computing theproduct of V_(R) and the compliance voltage margin, and then computingthe adjusted compliance voltage as the sum of this product, the tissuevoltage drop V_(R), the capacitor voltage V_(cx), V_(cy), and thedesired operating voltage of the current source 62 and current sink 64to arrive at the adjusted compliance voltage V+. If the compliancevoltage margin takes the form of an absolute value, the microcontroller76 simply computes the adjusted compliance voltage as the sum of thecompliance voltage margin, the tissue voltage drop V_(R), the capacitorvoltage V_(cx), V_(cy), and the desired operating voltage of the currentsource 62 and current sink 64.

In an alternative embodiment, the microcontroller 76 determines thebaseline compliance voltage by directing the voltage regulator 118 toincrementally decrease the compliance voltage until the measured voltagedrop across the current source 62 and current sink 64 meets a thresholdvalue. In the illustrated embodiment, the compliance voltage isdecreased from a maximum value, and the threshold value is sum of theoperating voltages of the current source 62 and current sink 64, such asthe saturation voltages. This alternative technique is described in U.S.Pat. No. 8,175,719, which is expressly incorporated herein by reference.

As discussed above, the microcontroller 76 is also configured foradjusting the compliance voltage adjustment interval and compliancevoltage margin. These two parameters can be adjusted either in unison orindependently from each other. As briefly discussed above, themicrocontroller 76 may adjust either or both of the compliance voltageadjustment interval and compliance voltage margin by comparing afunction (e.g., the difference between two voltage drops determined attwo consecutive compliance voltage adjustment intervals, or an averageof the voltage drop differences determined between a plurality ofconsecutive voltage adjustment intervals) of voltage drops across anelement of the circuit illustrated in FIG. 10 and one or more thresholdvalues stored in the memory 82. In the preferred embodiment, the voltagedrop that dictates the adjustment of the compliance voltage adjustmentinterval and compliance voltage margin is the voltage drop V_(R) acrossthe tissue resistance R, since the voltage drop V_(R) may be moredirectly correlated to impedance changes in the tissue, and thus,provides a more accurate indication of when the compliance voltageadjustment interval and compliance voltage margin should be adjusted. Assuch, the voltage drop on which these adjustments are based ispreferably the tissue voltage V_(R). Of course, the voltage drop onwhich these adjustments are based may be the compliance voltage V+,which would represent a more conservative approach to the adjustment ofthe compliance voltage adjustment interval and the compliance voltagemargin.

Turning now to FIG. 11, an exemplary method 300 for automatically makingperiodic adjustments to the compliance voltage using the DBS system 10will now be described. For illustrative purposes, specific parameters ofthe compliance voltage calibration process discussed below will referback to those of FIG. 8. First, the compliance voltage calibrationprocess is initiated (step 302). As previously described, the compliancevoltage calibration process is initiated whenever the IPG 14 is turnedon or electrical energy having a new set of modulation parameters isdelivered to the tissue.

Next, the DBS system 10 measures a tissue voltage drop V_(R) across thetissue resistance R caused by the delivered electrical energy at thestart of the compliance voltage calibration process (step 304).

Next, the DBS system 10 adjusts the compliance voltage based on a highcompliance voltage margin typical for Period 1 (e.g., 10%) (step 306).As described previously, the DBS system 10 adjusts the compliancevoltage as a function of the compliance voltage margin (e.g., apercentage of one or more voltage drops in the IPG 14 or a fixed margin)on top of a baseline compliance voltage necessary to deliver theprogrammed electrical energy.

Next, the DBS system 10 measures the short-term tissue voltage dropV_(R) again after a short compliance voltage adjustment intervalassociated with Period 1 (e.g., 1 minute) has elapsed (step 308). Asdiscussed above, the short-term tissue voltage drops V_(R), in theillustrated embodiment, refer to tissue voltage drops V_(R) measuredafter every compliance voltage adjustment interval.

Next, to determine how fast the short-term impedance is changing, theDBS system 10 computes a function of the short-term tissue voltage dropsV_(R) (step 310). As described previously, the computed function may bea difference between two consecutively measured tissue voltage dropsV_(R) or an average of the differences between recently-measuredconsecutive tissue voltage drops V_(R).

Next, the DBS system 10 compares the computed function of the short-termtissue voltage drops V_(R) to Short-term Threshold Value 1 (step 312).If the computed function is greater than Short-term Threshold Value 1(step 314), the DBS system 10 returns to adjusting the compliancevoltage based on the high compliance voltage margin associated withPeriod 1 (step 306).

If the computed function of the short-term tissue voltage drops V_(R) isequal to or less than Short-term Threshold Value 1 (step 314), the DBSsystem 10 adjusts the compliance voltage based on a moderate compliancevoltage margin typical for Period 2 (e.g., 5%) (step 316). Next, similarto the above-mentioned steps for Period 1, the DBS system 10 measuresthe short-term tissue voltage drop V_(R) after a moderate compliancevoltage adjustment interval (e.g., 5 minutes) associated with Period 2has elapsed (step 318), and computes a function of the short-term tissuevoltage drops V_(R) (step 320). Next, the DBS system 10 compares thecomputed function of the short-term tissue voltage drops V_(R) toShort-term Threshold Value 2 of the set of short-term threshold values(step 322).

Again, similar to the above-mentioned steps for Period 1, if thecomputed function of the short-term tissue voltage drops V_(R) isgreater than Short-term Threshold Value 2 (step 324), the DBS system 10returns to adjusting the compliance voltage based on the moderatecompliance voltage margin associated with Period 2 (step 316).

If the computed function of the short-term tissue voltage drops V_(R) isequal to or less than Short-term Threshold Value 2 (step 326), the DBSsystem 10 computes a function of long-term tissue voltage drops V_(R).As described previously, the long-term tissue voltage drops, in theillustrated embodiment, refer to tissue voltage drops V_(R) measureddaily from the point of implantation to track a long-term change intissue impedance. As was the case with short-term tissue voltage dropsV_(R), the computed function may be a difference between twoconsecutively measured daily tissue voltage drops V_(R) or an average ofthe differences between the most recently measured consecutive dailytissue voltage drops V_(R).

Next, to determine how fast the long-term impedance is changing, the DBSsystem 10 compares the computed function of the long-term tissue voltagedrops V_(R) to Long-term Threshold Value 1 (step 328). If the computedfunction of the long-term tissue voltage drops V_(R) is greater thanLong-term Threshold Value 1 (step 330), the DBS system 10 adjusts thecompliance voltage based on the compliance voltage margin associatedwith Period 3 a (long-term unstable impedance) (e.g., 3%) (step 332),and measures the long-term tissue voltage drop V_(R) after thecompliance voltage adjustment interval typical for Period 3 a (e.g., 4hours) has elapsed (step 334). Next, the DBS system 10 returns tocomputing a function of the long-term tissue voltage drops V_(R) (step326) to determine the rate of change of long-term impedance, andadjusting the compliance voltage based on the stability of the long-termimpedance.

If the computed function of the long-term tissue voltage drops V_(R) isequal to or less than Long-term Threshold Value 1 (step 336), the DBSsystem 10 adjusts the compliance voltage based on the compliance voltagemargin associated with Period 3 b (long-term stable impedance) (e.g.,2%) (step 338) and measures the long-term tissue voltage drop V_(R)after the compliance voltage adjustment interval typical for Period 3 b(e.g., 24 hours) has elapsed (step 338). Since the long-term impedancehas stabilized at this point, the DBS system 10 simply returns toadjusting the compliance voltage based on the compliance voltage margintypical for Period 3 b after every compliance voltage adjustmentinterval. The DBS system 10 continues to make these periodic adjustmentsto the compliance voltage margin until the IPG 14 is turned off or a newcompliance voltage calibration process is started.

It can be appreciated that by periodically adjusting the compliancevoltage, at varying compliance voltage adjustment intervals, based onvarying compliance voltage margins, the DBS system 10 automaticallycompensates for both short-term and long-term tissue impedance in anefficient manner. The compliance voltage calibration process ensuresthat the intended DBS therapy remains efficacious without unnecessarilywasting energy. Although the compliance voltage calibration process hasbeen described with respect to DBS therapy, it should be appreciatedthat this calibration process can be similarly utilized to calibrateother tissue modulation systems.

Although particular embodiments of the present inventions have beenshown and described, it will be understood that it is not intended tolimit the present inventions to the preferred embodiments, and it willbe obvious to those skilled in the art that various changes andmodifications may be made without departing from the spirit and scope ofthe present inventions. Thus, the present inventions are intended tocover alternatives, modifications, and equivalents, which may beincluded within the spirit and scope of the present inventions asdefined by the claims.

What is claimed is:
 1. A system for use with a plurality of electrodesimplanted within tissue, the system comprising: output circuitryconfigured to deliver electrical energy to at least some of theplurality of electrodes; a voltage regulator configured to supply acompliance voltage to the output circuitry; monitoring circuitryconfigured to determine a rate of change in tissue impedance; andcontrol/processing circuitry configured to automatically calibrate thecompliance voltage for the voltage regulator at a compliance voltageadjustment interval by adjusting the compliance voltage adjustmentinterval and a compliance voltage margin based on the determined rate ofchange in tissue impedance.
 2. The system of claim 1, wherein thecontrol/processing circuitry is configured to determine the compliancevoltage margin based on a voltage drop across tissue.
 3. The system ofclaim 1, wherein the control/processing circuitry is configured todetermine the compliance voltage margin based on a voltage drop acrossanalog circuitry.
 4. The system of claim 1, wherein thecontrol/processing circuitry is configured to determine the compliancevoltage margin based on at least one voltage drop generated by animplantable pulse generator.
 5. The system of claim 1, wherein thecontrol/processing circuitry is configured to maintain a firstcompliance voltage margin during a first time period, maintain a secondcompliance voltage margin during a second time period, and maintain athird compliance voltage margin during a third time period.
 6. Thesystem of claim 5, wherein the first compliance voltage is greater thanthe second compliance voltage and the second compliance voltage isgreater than the third compliance voltage.
 7. The system of claim 6,wherein the first time period is less than the second time period andthe second time period is less than the third time period.
 8. The systemof claim 1, wherein the control/processing circuitry is configured tomaintain a first compliance voltage adjustment interval during the firsttime period, maintain a second compliance voltage adjustment intervalduring the second time period, and maintain a third compliance voltageadjustment interval during the third time period.
 9. The system of claim8, wherein the first compliance voltage adjustment interval is less thanthe second compliance voltage adjustment interval and the secondcompliance voltage adjustment interval is less than the third compliancevoltage adjustment interval.
 10. The system of claim 1, wherein theoutput circuitry includes at least one of a current source and a currentsink configured for delivering the therapeutic electrical energy betweenthe electrical terminals, and the monitoring circuitry is configured formeasuring the voltage drop across the at least one of the current sourceand the current sink.
 11. The system of claim 10, wherein thecontrol/processing circuitry is configured to determine a voltage dropacross the tissue based on a difference between the compliance voltageand the measured voltage drop across the at least one of the currentsource and the current sink.
 12. The system of claim 11, furthercomprising a plurality of coupling capacitors, wherein the at least oneof the current source and the current sink is configured to delivertherapeutic electrical energy between the plurality of electricalterminals via the capacitors, the monitoring circuitry is configured tomonitor the voltage drops across the capacitors, and thecontrol/processing circuitry is configured to determine the voltage dropacross the tissue based on a difference between the compliance voltageand a sum of the measured voltage drop across the at least one of thecurrent source and the current sink and the measured voltage dropsacross the capacitors.
 13. The system of claim 12, wherein thecompliance voltage adjustment interval is adjusted from a value in therange of 0-20 minutes to a value in the range greater than 20 minutes,the compliance voltage margin is a voltage drop percentage, and thevoltage drop percentage is adjusted from a value in the range greaterthan 10% to a value less than 10%.
 14. The system of claim 12, whereinthe compliance voltage adjustment interval is adjusted from a value inthe range of 20-60 minutes to a value in the range greater than 60minutes, the compliance voltage margin is a voltage drop percentage, andthe voltage drop percentage is adjusted from a value in the rangebetween 5%-10% to a value less than 2%.
 15. The system of claim 12,wherein the compliance voltage adjustment interval is adjusted from avalue in the range of 60 minutes to 1 day to a value in the rangegreater than 1 day the compliance voltage margin is a voltage droppercentage, and the voltage drop percentage is adjusted from a value inthe range between 1%-2% to a value less than 1%.
 16. A method performedusing a system comprising output circuitry, a voltage regulator,monitoring circuitry, and control/processing circuitry, wherein themethod comprises: using the output circuitry to deliver electricalenergy to at least some of a plurality of electrodes implanted withintissue; using the voltage regulator to supply a compliance voltage tothe output circuitry; using the monitoring circuitry to determine a rateof change in tissue impedance; and using the control/processingcircuitry to automatically calibrate the compliance voltage for thevoltage regulator at a compliance voltage adjustment interval byadjusting the compliance voltage adjustment interval and a compliancevoltage margin based on the determined rate of change in tissueimpedance.
 17. The method of claim 16, further comprising using thecontrol/processing circuitry to maintain a first compliance voltagemargin during a first time period, maintain a second compliance voltagemargin during a second time period, and maintain a third compliancevoltage margin during a third time period.
 18. The method of claim 16,further comprising using the control/processing circuitry to maintain afirst compliance voltage adjustment interval during the first timeperiod, maintain a second compliance voltage adjustment interval duringthe second time period, and maintain a third compliance voltageadjustment interval during the third time period.
 19. A non-transitorymachine-readable medium including instructions, which when executed by amachine within a neuromodulation system that includes output circuitryand a voltage regulator, cause the machine to: use the output circuitryto deliver electrical energy to at least some of a plurality ofelectrodes implanted within tissue; use the voltage regulator to supplya compliance voltage to the output circuitry; determine a rate of changein tissue impedance; and automatically calibrate the compliance voltagefor the voltage regulator at a compliance voltage adjustment interval byadjusting the compliance voltage adjustment interval and a compliancevoltage margin based on the determined rate of change in tissueimpedance.
 20. The non-transitory machine-readable medium of claim 19,wherein the compliance voltage margin is determined based on a voltagedrop across tissue or a voltage drop across the output circuitry.